It is known that reduced coenzyme Q10 can be obtained, for example, by a method comprising producing coenzyme Q10 by a conventionally known method such as synthesis, fermentation, extraction from a naturally occurring substance and the like, and concentrating a reduced coenzyme Q10 fraction in an eluate from chromatography and the like (see patent reference 1). In this case, the Patent Publication describes that oxidized coenzyme Q10 contained in the above-mentioned reduced coenzyme Q10 can be reduced with a general reducing agent such as sodium borohydride, sodium hydrosulfite (sodium dithionite) and the like, and concentrated by chromatography, and that the reduced coenzyme Q10 can also be obtained by a method comprising reacting highly pure coenzyme Q10 containing the existing oxidized type as a main ingredient with the above-mentioned reducing agent.
However, the reduced coenzyme Q10 obtained as described above cannot be always obtained at high purity, and tends to be obtained, for example, as a crystal, an oily product or a semi-solid material of low purity containing impurities including oxidized coenzyme Q10.
The present inventors have conducted intensive studies, and as a result, they have established a production method for obtaining reduced coenzyme Q10 of high quality, and filed a patent application (for example, patent references 2 to 4).
However, reduced coenzyme Q10 is easily oxidized by molecular oxygen into oxidized coenzyme Q10, and even in a case where reduced coenzyme Q10 of high quality is produced by a method as described in the above-mentioned filed patent application, stabilization of reduced coenzyme Q10 has been remained as an important issue when it is processed into a food, food with nutrient function claims, food for specified health use, nutritional supplement, nutritional product, animal drug, drink, feed, cosmetic, pharmaceutical product, therapeutic drug, prophylactic drug and the like, or a material or composition therefor, and/or preserved after processing. Complete removal or blocking of oxygen during the above-mentioned processing and preservation is extremely difficult, and remaining or admixed oxygen particularly during heating for processing and long-term preservation exerts a markedly adverse effect. The above-mentioned oxidation is directly related to quality problems such as the by-product oxidized coenzyme Q10.
As mentioned above, stabilization of reduced coenzyme Q10 (protection from oxidation) is a highly important object. However, since reduced coenzyme Q10 is not commercially available to date, the study of methods and compositions for stable retention of reduced coenzyme Q10 has not been undertaken very much. As a conventionally method for stably retaining reduced coenzyme Q10, a method including addition of a reducing agent is known. However, some of the reducing agents used therefor are not suitable for food and pharmaceutical products, and many of reducing agents did not have sufficient objective stability.
For example, patent reference 5, which discloses a composition concurrently containing a reducing agent and a production method thereof, also discloses 1) a composition comprising reduced coenzyme Q10; a reducing agent in an amount effective for eliminating oxidation of reduced coenzyme Q10 into oxidized coenzyme Q10; a surfactant, vegetable oil or a mixture thereof in an amount effective for dissolving the above-mentioned reduced coenzyme Q10 and the above-mentioned reducing agent; and a solvent as necessary, 2) a composition for oral administration wherein the above-mentioned composition is prepared into a gelatin capsule or a tablet, and 3) a method of preparing the above-mentioned composition containing reduced coenzyme Q10 in situ using oxidized coenzyme Q10 and a reducing agent. However, no detailed description relating to the quality, stabilizing effect and the like of the reduced coenzyme Q10 contained in the composition is provided, and the expected level of stabilization is not clear.
In addition, the above-mentioned composition and preparation method thereof are highly complicated and complex since plural roles are conferred to the composition (i.e., firstly, a role as a reaction site for reducing oxidized coenzyme Q10 to reduced coenzyme Q10, and secondly, a role of stably retaining reduced coenzyme Q10). Moreover, the above-mentioned composition and a preparation method thereof are not entirely safe because the reaction mixture is used as it is.
In addition, ascorbic acids to be used as reducing agents are oxidized to produce a considerable amount of dehydroascorbic acids, and the dehydroascorbic acids get mixed in with the above-mentioned composition, posing a problem. Dehydroascorbic acids and oxalic acid produced by decomposition from dehydroascorbic acids are highly noxious, unlike ascorbic acids. For example, an increased amount of lipid peroxide and a decreased amount of antioxidants in the liver and kidney, and an increased amount of oxalic acid in the kidney have been reported, and side effects such as decreased resistance to oxidation stress, easy onset of ureteral lithiasis (non-patent reference 1) and the like are feared.
The present inventors considered that the above-mentioned problems have been solved, and have reported a composition which does not substantially inhibit stabilization of reduced coenzyme Q10 and contains reduced coenzyme Q10, fats and oils other than olive oil and/or a polyol, and if necessary, a polyglycerin fatty acid ester (patent reference 6), but the method does not always provide sufficient oxidative stability in a condition where further oxidative stability is required for long-term preservation or under a bad condition, and the like.    Patent reference 1: JP-A-10-109933    Patent reference 2: WO 03/06408    Patent reference 3: WO 03/06409    Patent reference 4: WO 03/32967    Patent reference 5: WO 01/52822    Patent reference 6: WO 03/062182    Non-patent reference 1: Nutriton Research, vol. 13, pp. 667-676, 1993Background Art